Immunoperoxidase techniques visualize specific antigens in paraffin-embedded tissues. The use of specific antibody can elucidate the nature of lesions that are obscure by light microscopy. For example, data presented in this proposal demonstrate that atypical cell of Kaposi's sarcoma derives from the endothelial cell, and that the atypical cell of Paget's disease contains the oncodevelopmental antigen, carcinoembryonic antigen, thus favoring a glandular origin for this cell. We outline projects that examine the spectrum of premalignant and malignant lesions in the skin using specific antibodies and the immunoperoxidase technique. Atypical lesions will be evaluated for the expression of oncodevelopmental antigens (carcinoembryonic antigen, alpha fetoprotein, HCG, ACTH, etc.) and for the loss of tissue-specific antigens and isoantigens. Histologically malignant but biologically benign lesions such as the keratoacanthoma, bowenoid papule of the penis and atypical fibroxanthoma will be studied with immunoperoxidase methods to see if they can be differentiated from true atypical hyperplasias. Immunoperoxidase methods will be employed using high titer antisera selected for antigens that are relevant to the analysis of the premalignant or malignant lesions (for example, anti-melanin antibody for the analysis of malignant spindle cell tumors, anti-carcinoembryonic antigen for the analysis of atypical clear cell lesions in the epidermis, etc.)